Introduction: Previous studies showed that continuous anticoagulation during implantation of cardiac rhythm device (CRD) was safe. However, the safety and efficacy of continuous anticoagulant and antiplatelet combination therapy in patients undergoing CRD interventions has not been clearly defined. Hypothesis: We sought to evaluate the safety and efficacy of this therapy during implantation of CRD. Methods: A total of consecutive 300 patients (mean 68.7 years old, 171 males) underwent CRD implantation were enrolled from April 2012 to December 2012. We divided patients into Non-drug (patients without antithrombotic therapy), Single-drug (patients with anticoagulant or antiplatelet therapy), and Combination-drug (patients with anticoagulant and antiplatelet therapy) group, and evaluated the clinical outcome among 3 groups. Clinically significant hematoma was defined as device-pocket hematoma that needed prolonged hospitalization, interruption of antithrombotic therapy, surgical intervention, or blood products transfusion. Results: The number of Non-drug, Single-drug, and Combination-drug groups was 129, 139, and 32, respectively. Clinical outcome was shown in Table. Hematoma occurred significantly more in Combination-drug than Non-drug group, but occurrence of clinically significant hematoma was not different among 3 groups. Cardiac tamponade was none and thrombo-embolic event was rare. Conclusions: Continuous anticoagulant and antiplatelet combination therapy was safe and effective during implantation of CRD.